Absolute Psoriasis Area And Severity Index Research Articles

A 3-Year Multicentric Study on Switching from Ustekinumab to Guselkumab in Partial Responders with Psoriasis-IL PSO (Italian Landscape Psoriasis).

Guselkumab, a human monoclonal antibody targeting the p19 subunit of interleukin-23 (IL-23), has shown efficacy in psoriasis and psoriatic arthritis. However, long-term real-world data on its effectiveness in patients with inadequate response to ustekinumab are limited. This study investigates guselkumab's long-term effectiveness and safety in patients with psoriasis with partial response to ustekinumab. We performed a retrospective multicentric study analyzing data of patients with psoriasis from seven Italian hospitals between January 2021 and May 2024. The study included 169 patients who switched from ustekinumab to guselkumab. Primary endpoints were Psoriasis Area and Severity Index (PASI) 75, PASI 90, PASI 100, and absolute PASI ≤ 2. Site-specific Physician Global Assessment (PGA) scores were also collected for difficult-to-treat areas. The study included 169 patients. After 3years of treatment, PASI 75, PASI 90 and PASI 100 were achieved by 88.4%, 55.8%, and 32.6% of patients, respectively. Site-specific PGA showed significant improvements, especially in the scalp and genital areas. After 3years of treatment, no significant impact of higher body mass index (BMI) or cardiometabolic comorbidities on guselkumab effectiveness was detected. No severe adverse events were reported during the study period. In our study, guselkumab provided significant long-term effectiveness and safety in patients partially responsive to ustekinumab, improving both PASI score and site-specific PGA and confirming its potential use for patients with psoriasis switching from ustekinumab.

Real-World Data on Brodalumab Treatment in Patients with Moderate-to-Severe Plaque Psoriasis: An Observational Study from the Czech Republic BIOREP Registry.

The aim of this observational, multicenter study was to assess the real-world use of brodalumab for the treatment of moderate-to-severe plaque psoriasis in patients in the Czech Republic, using data from the BIOREP registry. The study included 273 patients aged≥18years with moderate-to-severe psoriasis who received brodalumab. Endpoints were drug survival (time from treatment initiation to discontinuation), effectiveness [Psoriasis Area and Severity Index (PASI)], and health-related quality-of-life [Dermatology Life Quality Index (DLQI)]. Predicted drug survival probability was 92.4% [95% confidence interval (CI): 89.1, 95.7%] at 6months and 84.2% (95% CI 79.5, 89.1%) at 12months; this was maintained at 24months [80.4% (95% CI 74.5, 86.8%)]. Younger age, higher body mass index, and no previous biologic treatment were significantly associated with longer drug survival. Absolute PASI≤3 after 3months was achieved by 89.8% of patients; 92.4%, 77.8%, and 59.1% reached PASI 75, PASI 90, and PASI 100, respectively. After 12months, 96.5% of 141 patients had an absolute PASI≤3. The proportion of patients achieving DLQI 0/1 was 87.3% at 12months. This study demonstrated high and sustained drug survival with high rates of skin clearance and improved quality of life in patients with relatively severe disease treated with brodalumab. Improvements were observed as early as 3months post-treatment initiation and were sustained for up to 24months in a real-life setting.

Effectiveness and safety of secukinumab updosing in patients with moderate to severe plaque psoriasis: data from the PURE registry

Secukinumab is a fully human IgG1 antibody that selectively binds to and neutralizes the proinflammatory cytokine interleukin-17A. Secukinumab is an effective and well-tolerated treatment for plaque psoriasis. There is a limited real-word evidence for dose optimisation of secukinumab based on clinical response. PURE is a multi-national, prospective, observational study in patients with moderate to severe chronic plaque psoriasis in Canada and Latin America, assessing the real-world safety and effectiveness of secukinumab and other indicated therapies. The aim of the current snapshot analysis was to evaluate the effectiveness and safety of on-label dose and updosed secukinumab in patients with plaque psoriasis enrolled in the PURE study. At the time of analysis, 676 patients received secukinumab, of which 84.6% (n = 572) remained on the on-label dose, while 15.4% (n = 104) were updosed. With on-label secukinumab, the absolute Psoriasis Area and Severity Index (PASI) score was reduced from 13.6 at baseline to 1.2 over 36 months, with treatment persistence of 73% at 40 months. At Month 36, 73.2% of the patients receiving on-label secukinumab achieved Investigator’s Global Assessment (IGA) 0/1. With updosed secukinumab (300 mg every 2 weeks, 300 mg every 3 weeks, 450 mg every 4 weeks, or 450 mg every 3 weeks), 57.9% of the patients showed improvement in the absolute PASI score at the first visit after updosing, with treatment persistence of 50% at 12 months after updosing. At Month 15, 40% of patients receiving updosed secukinumab achieved IGA 0/1. Patients with previous biologic exposure (odds ratio [OR]: 3.25; 95% confidence interval [CI]: 2.03, 5.18, p < 0.0001) were more likely to be updosed while those with a body weight < 90 kg (OR: 0.49; 95% CI [0.31, 0.77], p = 0.0019) were less likely to be updosed. Previous biologic exposure (HR [hazard ratio]: 1.47; 95% CI [1.24, 1.75], p < 0.0001) and current biologic exposure (secukinumab vs. other indicated therapies: HR 0.57; 95% CI [0.43, 0.75], p = 0.0001) were significantly associated with time to secukinumab updosing. No new or unexpected safety signals were observed with updosed secukinumab. Secukinumab updosing was efficacious and well-tolerated in patients with psoriasis who failed to respond to the approved on-label regimen, suggesting that updosing may be a useful therapeutic option for approved dose non-responders.

Disease severity, treatment patterns, and quality of life in patients with moderate-to-severe psoriasis routinely managed with systemic treatment: results of the CRYSTAL observational study in Central and Eastern European countries.

Psoriasis is a common, life-long skin disease with a significant negative health and societal impact. Data on rates of disease control and treatment strategies are lacking in Central and Eastern European countries. We aimed to describe the real-world disease severity, control, and treatment strategies for psoriasis in patients from Central and Eastern European countries. CRYSTAL (EUPAS36459) was a cross-sectional, retrospective study in adults (18-75 years) from Bulgaria, Estonia, Hungary, Latvia, Lithuania, Romania, and Russia. We enrolled patients with moderate-to-severe psoriasis receiving continuous systemic treatment for ≥24 weeks. We used the Psoriasis Area and Severity Index (PASI) to describe disease severity and the Dermatology Life Quality Index (DLQI) to assess quality of life (QoL) and collected other outcomes [psoriasis work productivity and activity impairment (WPAI-PSO), patient satisfaction] at enrollment. Analyses were descriptive. A total of 690 patients were included in the analyses. Median disease duration was 11.8 years. Current treatment was monotherapy for most patients (95.8%) with either biological (BIO group; 88.4%) or conventional (NON-BIO group; 7.4%) agents. Mean (± standard deviation) absolute PASI scores were 3.5 ± 5.7, 3.1 ± 5.3, and 6.6 ± 7.4 in the overall population, the BIO group, and the NON-BIO group, respectively. Among patients treated with monotherapy, absolute PASI scores ≤1, ≤3, and ≤5 were observed for 44.1%, 72.0%, and 82.6% of BIO patients and 21.6%, 33.3%, and 49.0% of NON-BIO patients. Mean DLQI total score was 3.3 ± 5.1; higher scores were noted for higher absolute PASI. The most impacted WPAI-PSO domain was presenteeism; for all domains, impact increased with increased absolute PASI. A total of 91.8% of BIO patients and 74.5% of NON-BIO patients were satisfied with the current treatment. We observed a better disease control in BIO than NON-BIO patients. However, around half of BIO patients did not reach clear skin status and reported an impact on QoL. An improvement in treatment strategies is still needed in Central and Eastern European countries to optimize outcomes of moderate-to-severe psoriasis.

Real-world effectiveness and safety of bimekizumab in Japanese patients with psoriasis: A single-center retrospective study.

Bimekizumab, which suppresses both interleukin (IL)-17A and IL-17F, has recently been approved as a biologic for psoriasis. We aimed to evaluate the real-world effectiveness and safety of bimekizumab for psoriasis and to identify predictive factors for its treatment responsiveness. We analyzed 36 Japanese patients with psoriasis (19 with psoriasis vulgaris and 17 with psoriatic arthritis) from May 2022 to September 2023. All patients received bimekizumab (320 mg every 4 weeks) until week 16. Seventeen patients (43.2%) had experienced bio-switch. The median (interquartile range) baseline total psoriasis area and severity index (PASI) was 6 (3.2-20.0). Total PASI rapidly and significantly decreased at week 4 by a median 79.8% from baseline, and gradually decreased thereafter. The PASI on the trunk, and upper and lower limbs rapidly and significantly decreased at week 4 compared to baseline and plateaued thereafter. The neutrophil-to-lymphocyte ratio and neutrophil number significantly decreased at week 16 compared to baseline. At weeks 4, 8, 12, and 16, the achievement rate of absolute PASI ≤2 was 72.2%, 80.6%, 92.9%, and 96.4%, respectively; that of absolute PASI ≤1 was 41.7%, 61.3%, 85.7%, and 82.1%; that of PASI 75 was 55.5%, 52.9%, 69.7%, and 75.8%; that of PASI 90 was 36.1%, 50.0%, 57.6%, and 62.9%; and that of PASI 100 was 19.4%, 38.2%, 51.5%, or 57.6%, respectively. Linear multivariate regression analysis revealed that younger age was associated with a higher percentage reduction of total PASI at weeks 4 and 8. There were no serious or fatal adverse events during treatment. In conclusion, bimekizumab rapidly and remarkably reduced the total PASI together with high achievement rates of absolute PASI ≤1 and ≤2, and with favorable safety in real-world clinical practice. Younger age may be a predictive factor for a good treatment response to bimekizumab.

Association between several immune response-related genes and the effectiveness of biological treatments in patients with moderate-to-severe psoriasis.

Biological therapies are safer and more effective against psoriasis than conventional treatments. Even so, 30-50% of psoriatic patients show an inadequate response, which is associated with individual genetic heterogeneity. Pharmacogenetic studies have identified several single nucleotide polymorphisms (SNPs) as possible predictive and prognostic biomarkers for psoriasis treatment response. The objective of this study was to determine the link between several SNPs and the clinical response to biological therapies in patients with moderate-severe psoriasis. A set of 21 SNPs related to psoriasis and/or other immunological diseases were selected and analysed from salivary samples of patients (n = 88). Treatment effectiveness and patient improvement was assessed clinically through Relative Psoriasis Area and Severity Index (PASI), also called 'PASI response', as well as absolute PASI. Associations between SNPs and PASI factors were assessed at 3 and 12 months for every treatment category of IL-17, IL-23, IL-12&23 and TNF-α inhibitors. Multivariate correlation analysis and Fisher's exact test were used to analyse the relationship between SNPs and therapy outcomes. Several SNPs located in the TLR2, TLR5, TIRAP, HLA-C, IL12B, SLC12A8, TNFAIP3 and PGLYRP4 genes demonstrated association with increased short and long-term therapy-effectiveness rates. Most patients achieved values of PASI response ≥75 or absolute PASI<1, regardless of the biological treatment administered. In conclusion, we demonstrate a relationship between different SNPs and both short- and especially long-term effectiveness of biological treatment in terms of PASI. These polymorphisms may be used as predictive markers of treatment response in patients with moderate-to-severe psoriasis, providing personalized treatment.

Real-world safety and effectiveness of secukinumab in adult patients with moderate to severe plaque psoriasis: results from postmarketing surveillance in Korea.

Secukinumab, a fully human monoclonal antibody, was approved in Korea for the treatment of moderate to severe psoriasis in September 2015. To assess the safety and effectiveness of secukinumab in patients with moderate to severe psoriasis in Korea. Multicenter, real-world, noninterventional study conducted over 6 years. Adults with moderate to severe psoriasis were enrolled. Safety was assessed by evaluating adverse events (AEs), treatment-related AEs, and serious AEs (SAEs). Effectiveness was assessed using the change in absolute Psoriasis Area and Severity Index (PASI) score, percentage of patients achieving PASI 75/90/100 and PASI ⩽2; at weeks 12 and 24. Overall, 829 and 542 patients were included in the safety and effectiveness sets, respectively. AEs, treatment-related AEs, and SAEs occurred in 29.0%, 9.5%, and 4.1% of patients, with incidence rates of 39.43, 12.98, and 5.59 per 100 patient years, respectively. The absolute PASI score decreased from 16.1 ± 7.1 (baseline) to 1.6 ± 2.4 (week 24), with a similar reduction in biologic-naïve (16.4 ± 7.3 to 1.5 ± 2.2) and biologic-experienced (14.8 ± 5.9 to 2.4 ± 3.2) groups. At week 24, PASI 75/90/100 was achieved by 95.1%, 62.4%, and 24.9% of patients. At week 24, PASI 75/90 were higher in biologic-naïve (96.6%/65.8%) than biologic-experienced patients (88.3%/48.6%), whereas PASI 100 was similar in both cohorts (24.1% and 28.6%). A similar trend in PASI ⩽ 2 was observed in both cohorts. Secukinumab showed sustained effectiveness and favorable safety profile in adult patients with moderate to severe psoriasis in Korea.

Long-Term Drug Survival and Effectiveness of Secukinumab in Patients with Moderate to Severe Chronic Plaque Psoriasis: 42-Month Results from the SUPREME 2.0 Study.

SUPREME, a phase IIIb study conducted in Italy, demonstrated safety and high efficacy of secukinumab for up to 72 weeks in patients with moderate-to-severe plaque-type psoriasis. SUPREME 2.0 study aimed to provide real-world data on the long-term drug survival and effectiveness of secukinumab beyond 72 weeks. SUPREME 2.0 is a retrospective observational chart review study conducted in patients previously enrolled in SUPREME study. After the end of the SUPREME study, eligible patients continued treatment as per clinical practice, and their effectiveness and drug survival data were retrieved from medical charts. Of the 415 patients enrolled in the SUPREME study, 297 were included in SUPREME 2.0; of which, 210 (70.7%) continued secukinumab treatment throughout the 42-month observation period. Patients in the biologic-naïve cohort had higher drug survival than those in the biologic-experienced cohort (74.9% vs 61.7%), while HLA-Cw6-positive and HLA-Cw6-negative patients showed similar drug survival (69.3% and 71.9%). After 42 months, Psoriasis Area and Severity Index (PASI) 90 was achieved by 79.6% of patients overall; with a similar proportion of biologic-naïve and biologic-experienced patients achieving PASI90 (79.8% and 79.1%). The mean absolute PASI score reduced from 21.94 to 1.38 in the overall population, 21.90 to 1.24 in biologic-naïve and 22.03 to 1.77 in biologic-experienced patients after 42 months. The decrease in the absolute PASI score was comparable between HLA-Cw6-positive and HLA-Cw6-negative patients. The baseline Dermatology Life Quality Index scores also decreased in the overall patients (10.5 to 2.32) and across all study sub-groups after 42 months. Safety was consistent with the known profile of secukinumab, with no new findings. In this real-world cohort study, secukinumab showed consistently high long-term drug survival and effectiveness with a favourable safety profile.

Deucravacitinib, an Oral, Selective, Allosteric Tyrosine Kinase 2 Inhibitor, in Moderate to Severe Plaque Psoriasis: Absolute PASI Outcomes Over 52 Weeks in the Phase 3 POETYK PSO-1 Trial

Introduction: Tyrosine kinase 2 (TYK2) is an intracellular enzyme that mediates signaling of cytokines (eg, interleukin-23, Type I interferons) involved in psoriasis pathogenesis. Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in the US, EU, and other countries for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. In POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751), deucravacitinib was significantly more effective vs placebo and apremilast based on multiple endpoints. This study compared efficacy of deucravacitinib vs apremilast over 24 weeks in mean Psoriasis Area and Severity Index (PASI) improvements and evaluated absolute PASI thresholds with continuous deucravacitinib treatment from Day 1 through 52 weeks in PSO-1.&#x0D; Methods: PSO-1 randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily; patients randomized to placebo and apremilast switched to deucravacitinib at Week 16 and Week 24, respectively. Mean change from baseline in PASI and proportions of patients achieving absolute PASI thresholds of ≤1, ≤2, ≤3, ≤4, and ≤5 were evaluated at Week 24 (deucravacitinib vs apremilast) and Week 52 (deucravacitinib only).&#x0D; Results: Mean baseline PASI was similar in both groups (deucravacitinib, 21.8; apremilast, 21.4). Significantly greater mean percent reductions from baseline in PASI were observed with deucravacitinib vs apremilast at Week 24 (−77.1% vs −50.2%; P &lt; 0.0001); mean reduction in the deucravacitinib group was maintained through Week 52 (−78.4%). Higher proportions of patients receiving deucravacitinib vs apremilast, respectively, achieved absolute PASI thresholds of ≤1 (31.3% vs 12.5%), ≤2 (41.3% vs 21.4%), ≤3 (54.8% vs 28.0%), ≤4 (63.3% vs 33.3%), and ≤5 (68.7% vs 35.7%) at Week 24 (nominal P &lt; 0.0001 for all); response rates were maintained through Week 52 with deucravacitinib (31.3%, 45.5%, 54.5%, 61.4%, and 66.0%, respectively).&#x0D; Conclusions: Deucravacitinib treatment was associated with clinically meaningful PASI outcomes that were superior to apremilast over 24 weeks and maintained through 52 weeks in patients with moderate to severe plaque psoriasis.

Artículo traducido] Gravedad de la psoriasis, calidad de vida relacionada con la salud, productividad laboral y deterioro de la actividad en pacientes con psoriasis moderada a grave que reciben tratamiento sistémico: datos de la vida real de la práctica clínica en España

Background and objectiveThe treatment of psoriasis should not only focus on skin affectations but also weigh the parameters for health-related quality of life (HRQoL), thereby tackling the concept of cumulative life course impairment (CLCI) and treating the patient from a holistic perspective. The CRYSTAL study aimed to characterize psoriasis with real-word data from Spanish clinical practice in patients with moderate to severe disease who received continuous systemic treatment for at least 24 weeks by using the absolute Psoriasis Area and Severity Index (PASI) score and its correlation to HRQoL. Material and methodsThis was a non-interventional, cross-sectional study conducted in 30 centers in Spain, with 301 patients between the ages of 18 and 75 years. The study collected data regarding current treatment and absolute PASI and their relationship to HRQoL using the Dermatology Life Quality Index (DLQI), to activity impairment using the Work Productivity and Activity Impairment (WPAI) questionnaire, and to treatment satisfaction. ResultsThe mean (SD) age was 50.5 (12.5) years, with a duration of disease of 14 (14.1) years. The mean (SD) absolute PASI reported was 2.3 (3.5), with 28.7% of patients presenting with PASI from >1 to ≤3 and 22.6% with PASI>3. Higher PASI scores were associated with higher DLQI (p<0.001) and WPAI scores and lower levels of treatment satisfaction (p<0.001). ConclusionsThese data indicate that achieving lower absolute PASI values may correlate not only with better HRQoL but also with better work productivity and treatment satisfaction.

Acuerdo de riesgo compartido basado en resultados de salud para el tratamiento de psoriasis moderada-grave con certolizumab pegol

ObjectiveTo provide evidence of the effectiveness of certolizumab pegol (CZP) in real clinical practice in adult patients with moderate-to-severe plaque psoriasis (PsO) in the context of a risk-sharing agreement (RSA). MethodsRetrospective observational study based on variables collected in the RSA for treatment with CZP of adult patients with moderate-severe plaque PsO. Ten Spanish hospitals where the RSA was implemented participated. The percentage of patients who achieved the target clinical response of the RSA at the follow-up visit (week 16) was evaluated: absolute Psoriasis Area and Severity Index (PASI) value ≤3 for biologic naïve population, and ≤5 in case of previous failure to a single biologic drug. In addition, the improvement in the scores of other scales included in the study was analyzed: Body Surface Area (BSA), Dermatology Life Quality Index (DLQI), Physician's Global Assessment (PGA), and Nail Psoriasis Severity Index (NAPSI). A descriptive analysis was performed for the total population and by patient subgroups (naive vs. non-naive to biologic, male vs. female, and with vs. without discontinuation). ResultsSixty-six patients were included, 12 men and 54 women. 90.9% achieved the target clinical response, with a mean reduction of 8 (−78.4%) absolute PASI points. Improvement was observed in BSA, PGA, NAPSI and DLQI, with a reduction of 11.3 (−80.6%), 1.9 (−65.5%), 3.3 (−30.7%) and 9.0 (−66.4%) absolute value points, respectively. Despite not achieving the therapeutic target set in the RSA in six patients (9%) (the cost of the drug was assumed by the laboratory), only two (3%) discontinued treatment. ConclusionOur study shows that CZP is effective in real clinical practice in patients with moderate-severe plaque PsO, with an improvement in absolute PASI and DLQI, as well as other scales, both for the total population and in the subgroups analyzed. Nearly 91% of patients reached the therapeutic target fixed in the RSA. Implementing this type of agreement can provide a direct or indirect benefit for all the agents involved in the process, providing valuable information for decision-making.

Psoriasis Severity, Health-Related Quality of Life, Work Productivity, and Activity Impairments Among Patients With Moderate to Severe Psoriasis Receiving Systemic Treatment: Real-World Data From Clinical Practice in Spain

Background and objectiveThe treatment of psoriasis should not only focus on skin affectations but also weigh the parameters for health-related quality of life (HRQoL), thereby tackling the concept of cumulative life course impairment (CLCI) and treating the patient from a holistic perspective. The CRYSTAL study aimed to characterize psoriasis with real-word data from Spanish clinical practice in patients with moderate to severe disease who received continuous systemic treatment for at least 24 weeks by using the absolute Psoriasis Area and Severity Index (PASI) score and its correlation to HRQoL. Material and methodsThis was a non-interventional, cross-sectional study conducted in 30 centers in Spain, with 301 patients between the ages of 18 and 75 years. The study collected data regarding current treatment and absolute PASI and their relationship to HRQoL using the Dermatology Life Quality Index (DLQI), to activity impairment using the Work Productivity and Activity Impairment (WPAI) questionnaire, and to treatment satisfaction. ResultsThe mean (SD) age was 50.5 (12.5) years, with a duration of disease of 14 (14.1) years. The mean (SD) absolute PASI reported was 2.3 (3.5), with 28.7% of patients presenting with PASI from >1 to ≤3 and 22.6% with PASI>3. Higher PASI scores were associated with higher DLQI (p<0.001) and WPAI scores and lower levels of treatment satisfaction (p<0.001). ConclusionsThese data indicate that achieving lower absolute PASI values may correlate not only with better HRQoL but also with better work productivity and treatment satisfaction.

Brodalumab for the treatment of plaque psoriasis in a real-life setting: a 3 years multicenter retrospective study-IL PSO (Italian landscape psoriasis).

Brodalumab is a monoclonal antibody that targets the subunit A of the interleukin-17A receptor (IL17RA), inhibiting the signaling of various isoforms of the IL-17 family. It has been approved for the treatment of moderate-to-severe plaque psoriasis after being evaluated in three Phase-3 trials. However, long-term data on brodalumab in a real-life setting are still limited. The aim of this study was to evaluate the long-term effectiveness and safety of brodalumab in psoriasis. We also assessed the drug survival of brodalumab in a 3 years timespan. We conducted a retrospective multicenter study on 606 patients followed up at 14 Italian dermatology units, all treated with brodalumab according to Italian guidelines. Patients' demographics and disease characteristics were retrieved from electronic databases. At baseline and weeks 12, 24, 52, 104 and 156, we evaluated the psoriasis area and severity index (PASI) score and investigated for adverse events. The proportions of patients reaching 75, 90 and 100% (PASI 75, PASI 90 and PASI 100, respectively) improvement in PASI, compared with baseline, were also recorded. At week 12, 63.53% of the patients reached PASI 90 and 49.17% PASI 100. After 3 years of treatment, 65.22% of patients maintained a complete skin clearance, and 91.30% had an absolute PASI of 2 or less. Patients naïve to biological therapies had better clinical responses at weeks 12, 24 and 52. However, after 2 years of treatment, no significant differences were observed. Body mass index did not interfere with the effectiveness of brodalumab throughout the study. No new safety findings were recorded. After 36 months, 85.64% of our patients were still on treatment with brodalumab. Our data confirm the effectiveness and the safety of brodalumab in the largest real-life cohort to date, up to 156 weeks.

P77 Deucravacitinib, an oral selective allosteric tyrosine kinase 2 inhibitor, vs. placebo and apremilast in moderate-to-severe plaque psoriasis: achievement of absolute Psoriasis Area and Severity Index thresholds in two phase III trials

Abstract Deucravacitinib, an oral selective allosteric tyrosine kinase 2 inhibitor, is approved in the USA and several other countries and is under review by the European Medicines Agency and other health authorities, for the treatment of moderate-to-severe plaque psoriasis. The efficacy and safety results for deucravacitinib in the phase III, 52-week, double-blind POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials in patients with moderate-to-severe plaque psoriasis have been published (Armstrong AW, Gooderham M, Warren RB et al. Deucravacitinib vs. placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial. J Am Acad Dermatol 2023; 88:29–39; Strober B, Thaçi D, Sofen H et al. Deucravacitinib vs. placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 Program fOr Evaluation of TYK2 inhibitor psoriasis second trial. J Am Acad Dermatol 2023; 88:40–51). Additional efficacy outcomes using Psoriasis Area and Severity Index (PASI) measures were assessed. Patients were randomized 2 : 1 : 1 to oral deucravacitinib 6 mg once daily, placebo or apremilast 30 mg twice daily, with treatment switches at weeks 16 and 24 per study designs. Mean change from baseline PASI through to week 52, achievement of absolute PASI thresholds ≤ 3 and ≤ 4 at weeks 16 and 24 and proportions of patients treated continuously with deucravacitinib from day 1 who achieved absolute PASI thresholds ≤ 1, ≤ 2, ≤ 3, ≤ 4 and ≤ 5 at week 52 were determined. Mean baseline PASI was similar across groups in PSO-1 and PSO-2 (deucravacitinib, n = 332 and n = 511, respectively; placebo, n = 166 and n = 255; apremilast, n = 168 and n = 254). Mean change from baseline PASI (baseline mean 21.8) at peak efficacy at week 24 was −16.9 for PSO-1 patients treated continuously with deucravacitinib from day 1; decreases were maintained at week 52 (−17.1). At week 16, significantly higher proportions of deucravacitinib-treated patients vs. placebo and apremilast achieved absolute PASI thresholds ≤ 3 [PSO-1: 42.2%, 7.2% and 24.4%, respectively (P &amp;lt; 0.001 vs. placebo and apremilast); PSO-2: 40.9%, 6.7% and 29.5%, respectively (P &amp;lt; 0.001 vs. placebo and P = 0.002 vs. apremilast)] and ≤ 4 [PSO-1: 55.4%, 11.4% and 31.0%, respectively (P &amp;lt; 0.001 vs. placebo and apremilast); PSO-2: 49.5%, 9.4% and 37.4%, respectively (P &amp;lt; 0.001 vs. placebo and P = 0.001 vs. apremilast)]. Results were maintained for deucravacitinib vs. apremilast at week 24 (P &amp;lt; 0.001). Deucravacitinib patients treated continuously from day 1 achieved high rates of absolute PASI thresholds at week 52 in PSO-1 and PSO-2 (≤ 1, 31.3% and 23.4%, respectively; ≤ 2, 45.5% and 34.7%, respectively; ≤ 3, 54.5% and 44.0%, respectively; ≤ 4, 61.4% and 52.9%, respectively; ≤ 5, 66.0% and 59.5%, respectively). Patients with moderate-to-severe plaque psoriasis who received deucravacitinib achieved clinically meaningful absolute PASI outcomes superior to placebo and apremilast and showed good maintenance of these measures through to week 52. AcknowledgmentsWriting and editorial assistance was provided by Nick Cianciola PhD, CMPP, of Peloton Advantage, LLC, an OPEN Health company, funded by Bristol Myers Squibb. Funding sourcesThis study was sponsored by Bristol Myers Squibb.

P98 Real-world effectiveness of guselkumab in absolute Psoriasis Area and Severity Index-stratified patients with psoriasis: data from the British Association of Dermatologists Biologics and Immunomodulators Register

Abstract Guselkumab is a fully human monoclonal antibody that inhibits interleukin-23 by selectively targeting the p19 subunit. Long-term evaluations have demonstrated high levels of clinical response and improvement in patient-reported outcomes over 5 years of guselkumab treatment in patients with psoriasis. Psoriasis has a significant and negative impact on a patient’s quality of life, even among patients with a Psoriasis Area and Severity Index (PASI) score &amp;lt; 10. Both absolute PASI (aPASI) and the Dermatology Life Quality Index (DLQI) are widely used tools to assess disease impact, as well as treatment eligibility and response. This retrospective analysis evaluated the impact of guselkumab treatment over 1 year across aPASI-stratified patients with psoriasis in BADBIR, a national pharmacovigilance registry documenting longitudinal clinical data for individuals with psoriasis initiating systemic therapies. Retrospective analyses of the guselkumab cohort were carried out using BADBIR data collected up to September 2021. Data were analysed for patients who had initiated guselkumab treatment and had recorded aPASI and DLQI assessments at both baseline and the 12-month follow-up. Patients were stratified according to psoriasis severity at baseline: aPASI &amp;lt; 5, aPASI ≥ 5 to ≤ 10 and aPASI &amp;gt; 10 disease. Treatment effect was defined as the mean improvement in DLQI and aPASI scores for the overall group of guselkumab-treated patients and for subsets of patients with aPASI &amp;lt; 5, aPASI ≥ 5 to ≤ 10 and aPASI &amp;gt; 10 at baseline. Five patients were excluded owing to treatment cessation prior to the 12-month cutoff. Following 12 months of guselkumab treatment, patients with aPASI &amp;lt; 5, aPASI ≥ 5 to ≤ 10 and aPASI &amp;gt; 10 at baseline achieved a mean (SD) DLQI score of 2.18 (5.64), 2.79 (5.15) and 1.80 (3.56), representing a decrease of 62.0%, 74.8% and 89.1% from baseline, respectively. Additionally, patients with aPASI &amp;lt; 5, aPASI ≥ 5 to ≤ 10 and aPASI &amp;gt; 10 at baseline achieved a mean (SD) aPASI score of 0.96 (1.84), 3.16 (3.90) and 2.78 (4.93), representing a decrease of 40%, 58.6% and 84.5% from baseline, respectively. Among patients with an aPASI score &amp;lt; 10 at baseline (n = 53), 83.0% (n = 44) achieved aPASI score ≤ 3; of these, 67.9% (n = 36) achieved an aPASI score ≤ 2 and 54.7% (n = 29) achieved an aPASI score ≤ 1. These data demonstrate that guselkumab produces an effective and consistent response in patients with a broad range of disease severity at baseline, as reflected by mean improvements in aPASI and DLQI. Greater reductions in DLQI and aPASI scores were observed after 12 months of guselkumab treatment in patients with more severe psoriasis at baseline.

Efficacy and Safety of Secukinumab in Elderly Patients with Moderate to Severe Plaque-Type Psoriasis: Post-Hoc Analysis of the SUPREME Study.

Secukinumab is a fully human monoclonal antibody that inhibits interleukin (IL)-17A approved for the treatment of moderate to severe plaque psoriasis in adults and children. We compared the efficacy and safety of secukinumab in patients aged < 65 years (adult patients) versus patients aged ≥ 65 years (elderly patients) in a post-hoc analysis of the SUPREME study. Patients with moderate to severe plaque psoriasis received subcutaneous secukinumab 300 mg per week for the first 5 weeks, then 300 mg per month. We compared the following outcomes in patients aged ≥ 65 years vs < 65 years: baseline characteristics; PASI50/75/90/100 response rates (improvements ≥ 50%/75%/90%/100% in Psoriasis Area and Severity Index (PASI) from baseline); changes in Dermatology Life Quality Index (DLQI); Hospital Anxiety and Depression Scale (HAD-A, HAD-D) score changes; treatment-emergent adverse events (TEAEs). Secukinumab was slightly less effective in elderly patients than in adult patients (response rates at week 16: PASI90, 69.4% vs 80.9%, p = 0.4528; PASI100, 44.4% vs 56.7%, p = 0.8973). Elderly and adult patients showed a similar time course of changes in absolute PASI scores. Patients aged ≥ 65 years had a statistically significantly lower improvement in quality of life (mean DLQI reduction) than patients aged < 65 years at week 16 [-5.4 (±4.3) vs -8.8 (±6.9), p = 0.0065] and at week 24 [-5.3 (±4.4) vs -9.2 (±7.1), p = 0.0038]. Secukinumab treatment resulted in comparable mean reductions in anxiety and depression scores in both cohorts at 24 weeks [HAD-A, -1.3 (±3.3) vs -2.1 (±3.8), p = 0.9004; HAD-D, -1.0 (±3.3) vs -1.5 (±3.1), p = 0.4598]. The frequency of TEAEs in the two cohorts was similar (16.7% vs 14.6%, p = 0.7391). Secukinumab is a valid option for the management of moderate to severe psoriasis in elderly patients.

Long-Term Efficacy, Safety, and Drug Survival of Guselkumab in Patients with Psoriasis: Real-World Data from the Czech Republic BIOREP Registry.

Real-world data on the long-term use of guselkumab for treatment of psoriasis are still limited. We aimed to evaluate long-term efficacy, safety, and drug survival of guselkumab in a real-world setting. This is a retrospective study analyzing Czech Republic registry (BIOREP) data of patients treated with guselkumab. In total, 333 patients were included. Improvement in Psoriasis Area and Severity Index (PASI) score was significant. Mean PASI score decreased from 16 at baseline to 0.7, 0.9, and 0.8 after 12, 24, and 36months, respectively. Absolute PASI scores of ≤ 3 and ≤ 1 were achieved in 93.9% and 77.9%, 94.2% and 71.0%, and 94.8% and 70.7% of patients after 12, 24, and 36months, respectively. Response PASI 90 and PASI 100 were attained in 81.8% and 57.1%, 75.4% and 50.7%, and 75.9% and 55.2% of patients after 12, 24, and 36months, respectively. The percentage of patients achieving PASI 90 and PASI 100 responses was higher throughout the study in bio-naive and in normal-weight patients, while presence of psoriatic arthritis had no influence. Improvement in Dermatology Life Quality Index (DLQI) score was also significant; mean DLQI score decreased from 14.2 at baseline to 0.9, 1.0, and 0.7 after 12, 24, and 36months, respectively. Patients with PASI 100 had lower mean DLQI throughout the study compared with patients with PASI 90. Major reason for discontinuation was loss of effectiveness in 7.1% of patients, while only 0.6% were due to adverse events. Overall cumulative drug survival was high, with only a minimal decline over time, reaching 91.6%, 87.0%, and 85.5% after 12, 24, and 36months, respectively. Drug survival was not affected by previous biological treatment, patient weight, or presence of psoriatic arthritis. This real-world study demonstrated the long-term effectiveness, good safety profile, and high drug survival of guselkumab treatment over a period of 36months.

Bimekizumab Efficacy and Safety in Japanese Patients with Plaque Psoriasis in BE VIVID: A Phase 3, Ustekinumab and Placebo-Controlled Study.

Bimekizumab treatment resulted in improved clinical outcomes in patients with moderate-to-severe plaque psoriasis in BE VIVID, a 52-week, phase 3, randomized, ustekinumab and placebo-controlled study. We present data from the BE VIVID Japan patient subpopulation. Globally, patients were randomized to receive bimekizumab 320mg every 4weeks (Q4W), ustekinumab (45/90mg weight-based at baseline and week 4, then every 12weeks), or placebo (Q4W through week 16, then bimekizumab 320mg Q4W). Efficacy endpoints included week 16 Psoriasis Area and Severity Index (PASI) 90 and Investigator's Global Assessment (IGA) 0/1, and other outcomes [PASI 100, PASI 75, IGA 0, Dermatology Life Quality Index (DLQI) 0/1, absolute PASI, scalp IGA, Psoriasis Symptoms and Impacts Measure (P-SIM) responses]. Safety analyses were conducted. There were 108 Japanese randomized patients (bimekizumab: 62; ustekinumab: 29; placebo: 17). At week 16, bimekizumab-treated patients had a higher clinical response versus ustekinumab and placebo (PASI 90: 85.5% versus 51.7% and 5.9%; IGA 0/1: 82.3% versus 48.3% and 0.0%). Over 52weeks, improved clinical response was maintained with bimekizumab, including patients switching from placebo at week 16. Overall, the safety profile in Japanese patients was consistent with that observed in the global population. Bimekizumab resulted in improved clinical response versus ustekinumab and placebo, and was well-tolerated in Japanese patients. NCT03370133.

Real-Life Effectiveness and Safety of Risankizumab in 131 Patients Affected by Moderate-to-Severe Plaque Psoriasis: A 52-Week Retrospective Study.

IntroductionRisankizumab is a humanized monoclonal antibody that selectively targets interleukin-23. It is approved for treatment of moderate-to-severe plaque psoriasis. We conducted a 52-week monocentric retrospective study to evaluate the effectiveness and safety of risankizumab in a real-life setting.MethodsOur study included 131 adults with moderate-to-severe plaque psoriasis all treated with risankizumab for at least 52 weeks. Patient characteristics and PASI (Psoriasis Area and Severity Index) at each visit were recorded. The percentages of patients achieving 75%/90%/100% (PASI 75/90/100) improvement in PASI with respect to baseline were registered.ResultsAt week 52, 93.9%, 78.6%, and 61.1% of patients achieved PASI 75/90/100, respectively. An absolute PASI ≤ 2 was reached by 90.8% at week 52. The higher body mass index and the presence of cardio-metabolic comorbidities did not interfere with the odds of reaching PASI 75/90/100 at each time-point. At week 52, comparable percentages of patients achieved PASI 100, regardless of the involvement of difficult-to-treat-areas. No significant safety findings were recorded and none of the patients had to interrupt the treatment because of adverse events.ConclusionsOur findings confirmed that risankizumab is a safe and effective therapeutic option for the treatment of a wide “real-life” cohort of patients with psoriasis.

33025 Stability of PASI

Background: Tildrakizumab, a high-affinity anti–interleukin 23p19 monoclonal antibody approved for the treatment of moderate to severe plaque psoriasis, has demonstrated efficacy and safety for up to 5 years. Absolute Psoriasis Area and Severity Index (PASI) <3 is considered a clinically relevant treatment target for moderate to severe plaque psoriasis. We determined the percentages of patients in the Phase 3 reSURFACE 1/2 (NCT01722331/NCT01729754) trials with PASI <3 at ≥80% and all follow-up visits up to week (W) 244. Methods: Methodology of these randomized controlled trials was previously published. At W64/W52, patients with at least a PASI 50 response entered an optional 4-year extension up to W256 (reSURFACE 1)/W244 (reSURFACE 2). Tildrakizumab 100 and 200 mg were administered at W0, W4, and every 12W thereafter. Study population included patients with PASI <3 at W28 (PASI <3 responders) who were randomized to continue treatment. Missing data were handled using multiple imputation. Results: At W28, 263 and 180 PASI <3 responders receiving tildrakizumab 100 and 200 mg, respectively, continued treatment. The mean (SD) numbers of visits with an absolute PASI <3 were 16.0 (3.5) and 16.6 (3.3) for tildrakizumab 100 and 200 mg, respectively; the median for both was 18.0. Among responders receiving tildrakizumab 100 and 200 mg, 80.2% and 87.2%, respectively, maintained PASI <3 response at ≥80% of follow-up visits and 58.9% and 70.0%, respectively, at all scheduled follow-up visits through W244. Conclusions: Tildrakizumab provided steady disease control over 5 years in most patients who were PASI <3 responders at W28.